Between May 8 and 98, 2006, the United States Food and Drug Administration (FDA) conducted an inspection of your establishment at the above-referenced address. The FDA investigator determined that your firm manufactures and distributes the FIoProbe, a product that is placed in-line in the extracorporeal circuit to detect fluid flow during open-heart surgery; the FIoPump, a centrifugal blood pump assembly (a magnetic impeller integrally molded into a base of the polycarbonate housing) that,is used to pump blood through the extracorporeal bypass circuit during open-heart surgery; the Suction Handle, a wand that is used to aspirate blood during open-heart surgery, and the MediDerm Laser, a Erbium YAG solid-state laser that is used for skin resurfacing. These products are devices, as defined by section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 321 (h)).

The FDA's inspection revealed that your devices are adulterated within the meaning of Section 501(h) of the Act (21 U.S.C. § 351(h)) because the methods used in, or the facilities or controls used for the manufacturing, packing, storage, or installation are not in conformance with the Current Good Manufacturing Practice.(CGMP) requirements of the Quality System (QS) Regulation for medical devices, as specified in Title 21, Code of Federal Regulations (CFR), Part 820.

At the close of the inspection, FDA issued to your firm a list of Inspectional Observations, Form FDA-483 (copy enclosed), which identifies a number of significant violations, including, but not limited to, those described below.

QS Regulation

1. Failure to validate a process whose results cannot be fully verified by subsequent inspection and test, approve the validation according to established procedures, and document the validation activities and results, as required by 21 CFR § 820.75(a). FDA-483 Items 1, 2, and 3. For example, your firm has not:

a. Validated the heat sealing process used to seal the packaging of sterile medical devices. Your CAPA 2005-09, dated August 16, 2005, documented that your firm received a customer complaint of defective seals on the tyvek pouches containing sterile suction handles. Your firm instructed the customer to return their inventory of the affected devices for replacements. Your firm then tested its remaining inventory of these devices and found [redacted]% of them had defective seals. The entire device inventory was reworked by repackaging, resealing, and resterilizing. FDA-483 Item 1.

b. Documented the results of any inspection of the repackaged and resterilized suction handles r od nd pouch seal integrity. Your firm also failed to conduct [redacted] residual testing of the resterilized suction handles. Moreover, your firm's original validation of the [redacted] sterilization process did not explain or contain data to demonstrate whether or not the suction handles can be resterilized by multiple full sterilization cycles. FDA-483 Item 2.

c. Completely validated the injection -molding process used to manufacture the FloPump, FIoProbe, and Suction Handle. For example, two of the [redacted] injection molding machines have not been validated. Additionally, operational tolerances for injection molding settings (specifications) have not been, defined, tested, evaluated, and documented for acceptance during the initial validation. Records reviewed indicated that the nozzle temperature of each of the [redacted] zones deviated by 10° F between runs without establishing an acceptable tolerance.

d. Adequately validated, explained, and documented a series of changes in the injection molding settings prior to their implementation as reflected in your CAPA 2006-03, dated January 17, 2006. Your firm has received a number of complaints of cracks at the base of the FIoPumps since 2004. To address the crack issue, your firm made multiple changes to the injection molding production settings to manufacture a lot of the FIoPumps~and conducted stress tests of [redacted] samples from this lot between November 22, 2005 and December 5, 2005. The CAPA 2006-003 record indicated that two samples of the pumps tested on November 28 and 29, 2005 failed stress testing but did not explain if the pumps manufactured on these two specific dates were released for commercial distribution. On January 17, 2006 the Products and Materials Technician could not confirm whether or not and how the molding setups were changed between November 22, 2005 and December 5, 2005. FDA-483 Item 3.

2. Failure to implement and record changes in methods and procedures needed to correct and prevent identified quality problems, as required by 21 CFR 820.100(a)(5). FDA-483 Item 1. According to your CAPA 2005-08 Record, dated July 27, 2005 our firm's internal quality audit documented that your firm's heat sealing and [redacted] curing process needed to be validated. However, Section 5 of the CAPA Record concluded that the heat sealer could not be validated without explaining why. Your firm failed to take action to correct or explain why this quality audit deficiency was not corrected at the time of the current FDA inspection.

3. Failure to establish and maintain adequate procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 CFR.§ 820.80(d). FDA-483 Items 4, 5, and 6. For example:

a. Your firm has not documented a specific test range (a low and high value) for accepting or, rejecting the MediDerrn laser devices' laser outputs at the low, medium, and high input laser settings. Your production manager verbally stated that there is no established test range for the laser outputs without providing an appropriate scientific justification or a recognized standard. The production manager further stated that the laser handle's laser output should not exceed [redacted] millivoits (mv) during production testing. This maximum laser output specification was not documented. For example, the calibration record (calibration version 2.66), dated May, 7, 2004, for the Laser Handle LH) 1009-5 recorded a high laser output of [redacted] mv and [redacted] mv at [redacted] Hz and [redacted] Hz pulse frequency, respectively.

b. Your firm has not documented specific written test instructions/method(s) and specific test equipment to explain how the laser outputs of the laser handles and control units are consistently calibrated; measured or calculated, and accepted or rejected~during their production or during their subsequent returns to your firm for servicing or upgrades. For example, calibration records of the laser devices documented that employees performing the laser tests recorded various "low" "medium," and "high" laser input voltages, various time durations ranging from [redacted] to [redacted] minutes for laser firing, and various initial and average laser output values. There are no 'test ranges defined for these quality attributes. Additionally, calibration records did not document whether or not the laser handles were actually calibrated before or after burn-in. See the calibration records for LH 1049-5 (version 2.66, dated May 5, 2005), LH 1049-5 (version 2.68, dated March 6, 2006, laser device returned for servicing or upgrades), and LH 1009-5 (version 2.66, dated October 14, 2005).

4. Failure to review and approve acceptance records of finished devices for adequacy prior to releasing finished devices for distribution, as required 21 CFR § 820.80(d) and (e). FDA-483 Items 4, 5, 6. Calibration records of a number of the laser handles and control units documented irregularities in their test results. Your firm released these laser devices for distribution without maintaining adequate test records to demonstrate how the laser devices passed their approved specifications. For example:

a. Calibration record for Laser Handle LH 1009-5 (calibrated with version 2.68) documented that the laser handle was tested with a different laser control unit to see if the laser handle could be used, the laser pattern was not desirable in low frequency of [redacted] Hz, the laser handle was only running at a frequency [redacted] Hz with reprogramming of the laser control unit, and a high initial laser output [redacted] mv. There was no additional information explaining why the laser control unit was reprogrammed, how the laser handle and control unit were adjusted internally, retested for acceptance, approved, and released.

b. Calibration record for Laser Handle LH 1127-5 and Laser Control Unit CU 1027 (calibrated with version 2.68) documented that the laser outputs were somewhat erratic. There was no additional information explaining what was wrong with the laser devices, whether or how the laser devices were repaired or upgraded, retested for acceptance, approved, and released.

c. Calibration records for the Laser Handle LH 1144-5 and 1147-5 and Laser Control Unit CU 1947 (calibrated with version 2.68) and Laser Handle LH 1010-5 documented that the initial test results were lined through and new test results were recorded. It is uncertain which test results were valid and belong to the original built laser devices or the modified laser devices. These modified laser devices were destined for a foreign country. Specifics on the modifications were not clearly explained and documented.

5. Failure to maintain an adequate design history file for each type of device to demonstrate the design was developed following the approved design plan and the design requirements, as required by 21 CFR § 820.30(j). A review of the records in the design history file of the,MediDerm Model IVIED 500 laser device, the operator's manual of the laser device in the design history file, and calibration records of the production laser devices revealed possible changes in the design' requirements. Your firm has not updated the design history file to add additional design records which explain and document possible design changes. For example, the October 27, 2003 design review of the design outputs documented a maximum weight of [redacted] for the laser control unit (console). The operators manual in the design history file documented a console weight of [redacted]. The device's weights were conflicting, and the change in device's weight was not explained and documented in the design history file. A second example of a change in the laser devices involved wiring changes to the production of laser handles for export to [redacted]. This change was not explained and documented in the design history file. See calibration records for the production LH 1144-5, 1147-5, LH 1010-5 laser handles. A third example involved a change in the software calibration version used to calibrate production laser outputs (e.g. a change from software version 2.66 to 2.68) as documented in the calibration records.

6. Failure to establish and maintain procedures to ensure that formal documented reviews of the design results are planned and conducted at appropriate stages of the device's design development, and that the results of a design review shall be documented, as required by 21 CFR § 820.30(e). Your firm has not always documented the results of design reviews in adequate detail to determine the actual progress of a design stage and how a design stage was verified as complete. For example, the March 24, 2003 design review was held to discuss the MediDerm laser device's performance characteristics and delivery of ordered parts. The specific device components and specific device performance characteristics were not documented or referenced. In another instance, the December 18, 2003 design review was held to discuss the design verification tests and results. Your firm approved the design verification results but did not document what specific design verification results or design verification documents were reviewed and deliberated during the design review.

7. Failure to maintain device master records (DMR's) that include or refer to the location of device specifications, production process specifications, quality assurance procedures, packaging and labeling specifications; and failure to ensure that each DMR is prepared and approved in accordance with 21 CFR § 820.40. See 21 CFR § 820.181 and FDA-483 Item 5. Your device master record for the MediDerm laser device is incomplete in that (a) the test range of the device's laser outputs was not documented; and (b) the labeling requirements and the inspection of device labeling are not documented in the LSOP 003-02 Laser System Final Operational Testing and Packaging, dated May 4, 2006.

8. Failure to establish and maintain procedures to ensure that device history records for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record, as required by 21 CFR § 820.18.4. FDA-483 item 7. For example, your firm does not maintain copies of the primary identification label and labeling used for each MediDerm laser device.

9. Failure to establish and follow procedures for quality audits and conduct such audits to assure that your firm's quality system is in compliance with the established quality system requirements, as required by 21 CFR :§ 820.22. FDA483 Item 9 and 10. For example, (a) our firm's past quality audits have not been conducted within the required [redacted] time frame; (b) your audit procedure G1SOP-030-02, dated September 8, 2000, is deficient in that it does not identify all areas of the quality system to be audited (e.g. complaint handling, manufacturing process validation, design controls, CAPA, performance evaluation of suppliers, etc.); (c) two of the [redacted] injection molding machines have not been validated; and (d) individual(s) who conducted quality .audits have direct responsibility over the matters being audited. The quality assurance technician audited his own area of work, e.g. the incoming material inspections.

Medical Device Reporting Regulation

Additionally, the above-stated inspection revealed that your devices are misbranded under section 502(t)(2) of 'the Act, in that your firm failed or refused to furnish material or information required under section 519 respecting the device. Specifically, your firm failed to develop, maintain, and implement written medical device reporting (MDR) procedures as required by section 519 of the Act and 21 C FR 803.17. See FDA 483 Item 11.

Reports of Corrections and Removals

Your firm's sterile suction handles are also misbranded under section 502(t)(2) of the Act in that a report of correction or removal was not submitted to FDA as required by section 519(f)(1) of the Act. The Correction and Removal Regulation (21 CFR § 806), promulgated under section 519(f)(1), requires manufacturers or importers to promptly report to FDA any correction or removal of a device to reduce a risk to health within 10 working days. See 21 CPR § 806.10(a)(1); FDA-483 Item 8.

The inspection documented that on August 16, 2005 your firm received one complaint of defective seals on the tyvek pouches containing sterile suction handles and Instructed the customer to return its inventory of the affected devices for replacements. Your firm subsequently conducted seal testing of its in-house inventory of these devices and found [redacted]% of them had defective seals. Your entire inventory of the affected devices was reworked by repackaging, resealing, and resterilizing. See your CAPA 2005-09, dated August 16, 2005. Defective seals on the tyvek pouches may compromise the sterility of your sterile suction handles and potentially pose a risk to health. Your firm's action to retrieve the affected devices to prevent the use of unsterile devices meets the definition of a "removal in 21 CFR § 806.2(i), yet no report of the removal was submitted to FDA, in violation of 21 CFR § 806.10(a)(1), which requires manufacturers or importers to submit a written report to FDA of any correction or removal of a device if the correction or removal was irritated to reduce a risk to health.

Responding to This Letter

This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure adherence to each requirement of the Act and the regulations. The specific violations noted in this letter and in the Form FDA-483 may be symptomatic of other serious underlying problems in your firm's manufacturing and .quality assurance systems.

You must take immediate action to correct all violations of the Act and FDA regulations: Failure to promptly correct your firm's violations may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil penalties.

Federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, no applications for premarket approval to which the QS regulation deficiencies are reasonably related will be approved until the violations have been corrected. Also, no requests for Certificates to Foreign Governments will be approved until the violations related to the subject devices have been corrected.

Please notify, this office in writing within 15 working days of receipt of this letter of the specific steps you have taken or will take to identify and correct the noted violations, including (1) the timeframes within which the corrections will be completed, (2) any documentation indicating the corrections have been achieved, and (3) an explanation of each step being taken to identify and make corrections to any underlying systems problems necessary to ensure that similar violations will not recur.

Your response should be sent to Thao Ta, Compliance Officer, DAL-DO, Food and Drug Administration, HFR-SW140, 4040 N. Central Expressway, Suite 300, Dallas, TX 75240. If you have any questions about the contents of this letter, please contact Mr. Ta at 214- 253-5217.